BACTERIAL PATHOGENESIS

LECTURE 2
BLS 1st & 2ND YR 2008/09

A.S. HOZA

Why we do not get ill?

(i) the entire invading population is killed by phagocytic cells,
such as neutrophils, or circulating bacteriocidal compounds,
such as complement

(ii) the density of bacteria traversing the integument is

collectively too low to condition the tissue to allow their
population to grow or
(iii) the mutations or phase shifts required to get across the
mucosa or survive in the blood do not occur.

It is complex and strong stochastic

A.S. HOZA

Introduction
A pathogen is a microorganism that is able to cause disease in a
plant, animal or insect.
Pathogenicity is the ability to produce disease in a host
organism.

Microbes express their pathogenicity by means of their

virulence, a term which refers to the degree of pathogenicity of the
microbe.
Determinants of virulence of a pathogen are any of its genetic
or biochemical or structural features that enable it to produce
disease in a host.
A.S. HOZA

Introduction

The relationship between a host and a pathogen is dynamic, since

each modifies the activities and functions of the other.
The outcome of such a relationship depends on:
the virulence of the pathogen and
the relative degree of resistance or susceptibility of the host,
mainly due to the effectiveness of the host defense mechanisms.

A.S. HOZA

Animals and microbes

Normal flora (beneficial or ignored):

Virulent bacteria (actively cause disease):

A.S. HOZA

GI track, skin, upper respiratory track

pathogenic islands

Opportunistic bacteria (when host with underline problem):

Pseudomonas aeruginosa: cystic fibrosis/ burn

TB, Kaposis sarcoma (herpesvirus): AIDS

Mechanisms of Bacterial Pathogenicity

1. Invasiveness: the ability to invade tissues.
encompasses mechanisms for
colonization (adherence and initial multiplication),
production of extracellular substances which facilitate
invasion (invasins) and
ability to bypass or overcome host defense
mechanisms.

A.S. HOZA

Mechanisms of Bacterial Pathogenicity

2. Toxigenesis: ability to produce toxins.
Bacteria may produce two types of toxins:
i. exotoxins and
ii. endotoxins.
Exotoxins are released from bacterial cells and may act at
tissue sites removed from the site of bacterial growth.

Endotoxins are cell-associated substance. (classic sense,

endotoxin refers to the lipopolysaccharide component of the
outer membrane of Gram-negative bacteria).
A.S. HOZA

Mechanisms of Bacterial Pathogenicity

Endotoxins may be released from growing bacterial cells

and cells that are lysed as a result of effective host defense
(e.g. lysozyme) or the activities of certain antibiotics (e.g.
penicillins and cephalosporins).

Hence, bacterial toxins, both soluble and cell-associated,

may be transported by blood and lymph and cause cytotoxic
effects at tissue sites

Some bacterial toxins may also act at the site of colonization

and play a role in invasion.

A.S. HOZA

Animals and microbes

Normal flora (beneficial or ignored):

Virulent bacteria (actively cause disease):

A.S. HOZA

GI track, skin, upper respiratory track

pathogenic islands

Opportunistic bacteria (when host with underline problem):

Pseudomonas aeruginosa: cystic fibrosis/ burn

TB, Kaposis sarcoma (herpesvirus): AIDS

Big person in microbiology

Robert Koch,1843-1910, Germany

Kochs postulates:
1. suspected pathogen must be present
2. pathogen must be isolated and grown in pure culture
3. cultured pathogen must cause the disease
4. Same pathogen must be re-isolated from the subject
A.S. HOZA

Bacterial pathogenesis

Infection/entry

Virulence factors

Pathogenesis

Escape of immune surveillance

A.S. HOZA

Infection/entry

A.S. HOZA

Ingestion (fecal-oral)
Inhalation (respiratory)
Trauma (e.g burn)
Arthropod bite (zoonoses:
mosquito, flea, tick,
Tsetse fly)
Sexual transmission
Iatrogenic (needle stick,
blood transfusion)
Maternal-neonatal

Bacteria, virus, fungi

Ingestion: Salmonella, Shigella, Vibrio, Clostridium etc..

Inhalation: Mycobacterium, Mycoplasma, Chlamydia etc..
Trauma: Clostridium tetani
Arthropod bite: Rickettsia, Yersinia pestis, etc.

Sexual transmission: Neisseria gonorrboeae, HIV,

chlamydia, etc
Needle stick: Staphylococcus, HIV, HBV

Maternal-neonatal: HIV, HBV, Neisseria, etc.

A.S. HOZA

Modes of infectious disease transmission

Contact transmission

Direct contact (person-to-person): syphilis, gonorrhear, herpes

Indirect contact (fomites): enterovirus infection, measles
Droplet (less than 1 meter): whooping cough, strep throat

Vehicle transmission

Airborne: influenza, tuberculoses, chickenpox

Water-borne (fecal-oral infection): cholera, diarrhea
Food-borne: hepatitis, food poisoning, typhoid fever

Vector transmission

Biological vectors: malaria, plaque, yellow fever

Mechanical vectors: E. coli diarrhea, salmonellosis

A.S. HOZA

Extracellular versus Intracellular Parasitism

Extracellular parasites
destroyed when phagocytosed.
damaging tissues as they remain outside cells.
inducing the production of opsonizing antibodies, they

usually produce acute diseases of relatively short duration.

Intracellular parasites
can multiply within phagocytes.
frequently cause chronic disease.

A.S. HOZA

The environment in a cell

Cytosol: pH=7
Phagosome: pH=6
Phagolysosome: pH=5

Adapted from: http://bio.winona.msus.edu/bates/Bio241/images/figure-04-13b.jpg

A.S. HOZA

Barrier systems
Host cell
membrane

Taken up by
phagocyte
and resist killing

Inhibitory
molecule

Production
Of antibody

Degrade
antibody

IgA protease

Streptococcus

Antimicrobial
cell-mediated
response

Activate T cells
non-specifically
and
Productively

Superantigen

Staphylococcus

Antimicrobial
immune
response

Vary presenting
microbial
antigen

Switch on
production of
different
antigens

Borrelia

Genetic
recombination

Streptococcus

A.S. HOZA

Mycobacterium

Virulence factors
Factors enhancing the ability of bacteria to cause disease

Example: Pseudomonas aeruginosa

Adhesins: attachment

Alginate production: mucoid layer

Exotoxin A: inhibits host protein synthesis

Exoenzyme S: interferes with phagocytic killing

Elastolytic activity: degrades elastin

Phospholipase C: damages tissue

Pyocyanin: damages tissue by ROS

Antibiotic resistance: complicates therapy

A.S. HOZA

Pathogenic action of bacteria

Tissue destruction: flesh-eating bacteria:

Clostridium perfrigens
Obstruction: Cytic fibrosis
Toxins: bacterial components that directly
harm tissue or trigger disease symptoms

Endotoxin: lipopolysaccharides

Exotoxin: A-B toxins

Immunopathogenesis

Excess immune responses

Autoimmunity

A.S. HOZA

2. Endotoxins: heat stable

A.S. HOZA

Endotoxin: lipopolysaccharide
IL-1
TNF

Pseudomonas aeruginosa

Fever
Disseminated intravascular coagulation
Septic shock
death
A.S. HOZA

Superantigens
Secreted proteins
(exotoxins) that exhibit
highly potent lymphocytetransforming (mitogenic)
activity directed towards T
lymphocytes.

Polyclonal T cell activation

Aberrant cytokines,
cell death
A.S. HOZA

Antigen
/MHC-1

Specific T cell activation

Anti-microbes immunity

Known and suspected association of superantigens with

animal diseases
Autoimmune diseases
Lyme

disease
Multiple sclerosis
Acute diseases
Food

poisoning:
Staph infections
Streptococal

A.S. HOZA

EVASION STRATEGIES (1)

Defence

Microbial strategy

Mechanism

Example

Wash-out

Bind to cell

Adhesins

Neisseria

Inhibit ciliary
activity

Ciliotoxic/
Ciliostatic
molecule

Bordetella
Streptococcus

Disrupt
Chemotaxis
cytotoxic

Leucocidins

Staphylococcus

Inhibit
phagocytosis

Capsule

Streptococcus

Inhibit lysosomal
fusion

Inhibitory
molecule

Mycobacterium

Multiply

Unknown

Listeria

Ingestion
and
killing by
phagocyte

A.S. HOZA

EVASION STRATEGIES (2)

Defence

Microbial strategy

Mechanism

Example

Restrict FeLactoferrin
Transferrin

Compete

Siderophore

Mycobacterium
Escherichia

Activate
complement

A.S. HOZA

Interfere with
Fully sialylated
alternative pathway surface

Neisseria

Inactivate

Elastase

Pseudomonas

Antigen projects
beyond surface

Activation occurs
at the wrong site

Gram-negatives

Interfere with
complementmediated
phagocytosis

C3b receptor
competition,
microbe and
phagocyte

Streptococcus